Multicenter study of universal prophylaxis versus pre-emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation.

INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.

Elevated AT1R Antibody and Morbidity in Patients Bridged to Heart Transplant Using Continuous Flow Left Ventricular Assist Devices.

BACKGROUND: We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). METHODS AND RESULTS: Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2-5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2-9.2, P = .017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. CONCLUSIONS: In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.

Influence of physiological and psychological factors on cognitive dysfunction in heart failure patients.

AIM: Our study aimed to examine factors that contribute to cognitive dysfunction in patients with heart failure (HF). BACKGROUND: Although a majority of patients with HF have mild to moderate cognitive impairment, little is known about factors that influence progressive cognitive decline in this population. METHODS: We examined the influence of physiological factors (NYHA functional class II - IV, ejection fraction, co-morbidity burden, polypharmacy), psychosocial factors (anxiety, depression, evaluation for advanced therapy), and associated toxicities (anticholinergic drug burden), on cognitive dysfunction. Data were analyzed using mean (SE) for continuous variables and frequency and percent for categorical variables. Differences between NYHA functional classification (Class II vs. Class III/IV) were examined using Chi Square. Linear regression models were used to assess associations among model variables. RESULTS: Of the 113 participants with HF, Class III-IV HF were more cognitively impaired than those with NYHA Class II (p < 0.0001), had higher anxiety (p = 0.002), and depression (p = 0.003), and lower EF (p = 0.041). A majority of participants had a moderate anticholinergic drug burden, and NYHA Class III/IV participants had significantly higher medication counts than Class II participants (p = 0.034). Regression analysis found that NYHA Class III/IV, anxiety, depression and evaluation for advanced therapy significantly influenced cognitive dysfunction. CONCLUSIONS: Findings support a high prevalence of cognitive dysfunction, anxiety, and depression in NYHA class II-IV with a greater level of cognitive dysfunction in class III/IV patients.

Heart failure symptom clusters and functional status - a cross-sectional study.

AIM: To identify symptom clusters in individuals with heart failure and evaluate the relationship of the identified clusters to functional status. BACKGROUND: Heart Failure is a global health problem affecting approximately 1-2% of the adult population in developed countries worldwide. Individuals with heart failure may experience as many as nine symptoms and may limit activities that worsen their symptoms or adjust the way they engage in activities. DESIGN: Cross-sectional. METHODS: A convenience sample of individuals (n = 117) with a confirmed diagnosis of heart failure was recruited from an academic medical centre during 2011-2012. Prevalent heart failure symptoms and functional status outcomes (functional limitations and mobility) were evaluated. Factor analysis using the principal components method was used to extract symptom clusters. Regression analysis using a backwards stepwise model-building approach was used to examine the effects of the symptom clusters, age and co-morbidity on functional limitations and mobility. RESULTS: Three symptom clusters, sickness behaviour, discomforts of illness and gastrointestinal distress were extracted. When sickness behaviours and discomforts of illness were both present, functional limitations were more sensitive to sickness behaviours. Sickness behaviour and co-morbidity were related to limited mobility. CONCLUSIONS: Individuals with heart failure may be helped to improve their functional status by managing sickness behaviour and discomforts of illness symptoms. Identification of symptom clusters may lead to the development of interventions focusing on a cluster of heart failure symptoms.

Pregnancy-related allograft rejection following heart transplant.

Current recommendations do not discourage pregnancy in stable, orthotopic heart transplant (OHT) recipients who are more than 1 year posttransplant, although a highly specialized level of care with a multidisciplinary team is recommended. These patients may incur significant risk to themselves, their allograft, and/or their fetuses. Recognition and treatment of posttransplant complications in pregnancy also may be difficult. Although the risk of recurrent pregnancies in patients with peripartum cardiomyopathy (PPCM) is well defined, the risk of pregnancy after a PPCM patient has undergone OHT is unknown. A case of severe allograft rejection in a woman with a history of PPCM who became pregnant nearly 3 years after OHT is presented and her subsequent management is described. The data available on pregnancy after transplant are based on case reports, registry data, and reviews. The decision to become pregnant should be preceded by an extensive discussion including the patient, her partner, her obstetrician, and the transplant team, reviewing potential risks to her health as well as to her allograft and the fetus. Providers should be clear that many questions pertaining to pregnancy after transplant remain unanswered, and the patient should be comfortable going forward in this situation.

Living with a total artificial heart: patients' perspectives.

BACKGROUND: Advances in mechanical circulatory support have reduced morbidity and mortality in end-stage heart failure. To date, there have been no published studies examining the psychosocial impact on patients who are supported with a total artificial heart (TAH-t). PURPOSE: The purpose of this study was to describe the lived experience of patients currently supported by the TAH-t awaiting transplant. METHODS: A qualitative method using Giorgi's modification of phenomenologic inquiry guided the investigation, which was conducted at a transplant center located in the mid-Atlantic region of the United States. A purposive sample was selected to reflect participants currently supported by the TAH-t. All participants (9 men, 1 woman; mean age, 48.2 years; nonischemic etiology, 80%) were in-patients on the progressive care unit at the time of the interview and had been supported for at least 30 days. The mean length of device therapy was 84.7 days (range, 33-245 days). FINDINGS: Hope for the future was the overarching theme. Subthemes included reflections, for better or for worse, the secret club, and coping and adaptation. The patients reflected on severity of illness, progress, and expressed optimism. For better or for worse described how symptoms improved but were offset by restrictions imposed by the technology. The secret club described the support provided to help deal with their life situation. Coping and adaptation suggested that the patients came to terms with and accepted their circumstances. CONCLUSIONS: The findings will help clinicians understand patients experiencing a life-changing situation and implications for psychosocial interventions.

When Should Patients With Less Than 6 Months Sobriety Be Transplanted?

Alcoholic liver disease (ALD) and alcohol-induced deaths have increased dramatically over the last 2 decades. Patients are often referred to liver transplant programs critically ill with a life expectancy of less than 6 months. Historically, less than 6 months sobriety has been an absolute contraindication for transplant listing as ALD is stigmatized as a choice, as patients are responsible for their condition because they did not stop drinking. It has been recommended that 6 months of sobriety should not be considered the determining factor for access to transplantation. However, changing years of clinical practice involves developing new protocols, finding available resources, reworking systems, transforming team, and institutional culture. Steps taken by a large, urban, academic liver transplant program to develop a program for patients with end stage ALD with less than 6 months of sobriety are outlined.

Persistent anemia after implantation of the total artificial heart.

BACKGROUND: The total artificial heart (TAH) replaces the heart with 2 pneumatic pumps and 4 tilting disk mechanical valves. It was hypothesized that patients receiving TAH support have persistent hemolysis that resolves after heart transplantation (HT). METHODS AND RESULTS: Hematocrit (HCT) was compared in patients on TAH to left ventricular assist device (LVAD) support for bridge to HT. Data were compared with t tests. The TAH (n = 36; mean age 47 ± 13 years) and LVAD patients (n = 14; mean age 53 ± 12 years) were supported for a median of 83 (interquartile range [IQR] 43-115) and 106 days (IQR 84-134), respectively. Hematocrit was similar between the TAH and LVAD patients (34 ± 6% vs 37 ± 5%; P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 ± 2% vs 24 ± 3%), 4 (22 ± 3% vs 26 ± 3%), 6 (22 ± 4% vs 30 ± 4%), and 8 weeks (23 ± 4% vs 33 ± 5%; P < .001 for all). There were no differences in HCT at 1 (30 ± 4% vs 29 ± 7%; P = .42) and 3 months (35 ± 7% vs 35 ± 4%; P = .98) after removal of the devices for HT. TAH patients had undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 ± 384 units/L), and detectable plasma free hemoglobin in 40% of measurements (21 ± 15 mg/dL). High sensitivity C-reactive protein (52 ± 50 mg/dL) was elevated, and reticulocyte production index was decreased (1.6 ± 0.6). CONCLUSIONS: Patients implanted with a TAH have persistent anemia that resolves only after HT. The association of hemolysis, ineffective erythropoiesis, and inflammation with the TAH warrants further study.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Heart failure symptom clusters and quality of life.

BACKGROUND: Heart failure (HF) is a progressive symptomatic illness with reports suggesting that patients experience multiple symptoms. Symptom clusters constitute symptoms that co-occur, are related, and influence outcomes. OBJECTIVES: The specific aims of this study were to (1) examine prevalent symptoms experienced by persons with HF, (2) identify symptoms forming clusters, and (3) evaluate the impact of HF symptom clusters on quality of life (QOL). METHODS: 117 participants (62% male; 50% black; age = 56) were recruited. Prevalent symptoms were evaluated; principle components analysis (PCA) was used to extract symptom clusters; regression analysis was used to evaluate factors influencing QOL, defined as life satisfaction. RESULTS: Three symptom clusters-sickness behavior, discomforts of illness, and GI distress-were extracted. Sickness behavior significantly influenced QOL (ß = -0.603 p = 0.0001), explaining 40% of the variance (F = 75.12; R2 = 0.404; p = 0.0001). CONCLUSIONS: The Sickness Behavior cluster had a negative impact on QOL and suggests that incorporating an evaluation of these symptoms may facilitate identification and treatment of symptoms having an additive and detrimental influence on QOL. Studies to examine the stability of the clusters are warranted.

Community-based weight management in long-term heart transplant recipients: a pilot study.

BACKGROUND: Heart transplant recipients often suffer from obesity, dyslipidemia, and hypertension thought to be related to triple-drug immunosuppression and poor adherence to diet and exercise. A lifestyle intervention that allows recipients to attend a community-based weight management program may improve health outcomes. OBJECTIVE: To determine (1) the effects of attending a community-based weight management program on weight, systolic and diastolic blood pressure, and the lipid profile; and (2) the feasibility of a community-based program for weight management. METHODS: Twenty-one patients (81% male; age 57 years, 99.7 months since transplantation) participated in a randomized clinical trial and received either weight management counseling (control) or a 6-month scholarship to a structured commercial program (treatment). Using simple analysis of covariance models, group differences were assessed and reported as marginal means. RESULTS: At baseline, there were no demographic differences between groups. There were no differences in outcome variables except weight (control, 102.1 kg vs treatment, 98.3 kg; P= .05). After 6 months, significant differences were found in weight (control, 100.5 kg vs treatment, 95.6 kg; P= .047) and high-density lipoprotein cholesterol (control, 40.6 mg/dL vs treatment, 49.1 mg/dL; P= .044). A marginally significant difference was found in systolic blood pressure (control, 138 mm Hg vs treatment, 121 mm Hg; P= .07). A decrease in diastolic blood pressure (6 mm Hg) was attributed to treatment effect (P = .16). No differences were noted in total cholesterol, triglycerides, or low-density lipoprotein cholesterol. CONCLUSIONS: The structured commercial program appears to be an effective, feasible alternative to usual care. Findings need to be confirmed in future research with a larger sample.

Lifestyle and health status differ over time in long-term heart transplant recipients.

OBJECTIVE: To describe differences in lifestyle and health status across 5 post-transplant periods. METHODS: The sample consisted of 126 heart transplant recipients (87% men) grouped by time after transplantation: group 1, 12 to 24 months (n= 13); group 2, 25 to 48 months (n= 19); group 3, 49 to 72 months (n=24); group 4, 72 to 96 months (n=27); and group 5, > or =97 months (n=43). Data were obtained using demographic and health status evaluation forms and the Lifestyle Profile-II, which measures physical activity, nutrition, health responsibility, interpersonal relationships, stress management, and spiritual growth. RESULTS: Most often reported lifestyle attributes were spiritual growth and interpersonal relationships. Least often reported was physical activity. Pairwise comparisons revealed that groups 3 (chi2 = 16.4; SD = 4.8; P = .03) and 4 (chi2 = 16.6; SD= 5.8; P = .04) had lower physical activity than group 2 (chi2 = 21.3; SD = 5.2). Health status evaluation revealed that there were no group differences in systolic (P = .46) or diastolic (P = .77) blood pressure. Although creatinine was elevated, there were no group differences (P = .86). High-density lipoprotein was higher than 42 mg/dL in all groups, but there were differences across groups in low-density lipoprotein (P = .003). Groups 1 (chi2 = 139.2; SD = 38.5) and 2 (chi2 = 141.0; SD = 47.8) were different than group 5 (chi2 = 112.9; SD = 36.1; P = .05). There were group differences in cholesterol (P = .002), with lower levels in groups 4 (chi2 = 190.5; SD= 38.6) and 5 (chi2 = 186.3; SD = 37.7) as compared to group 2 (chi2 = 230.8; SD = 66.5). CONCLUSIONS: Identifying posttransplant periods in which healthy behaviors and health status may be vulnerable to decline is important for providing ongoing education and psychological support to transplant recipients who manage a complex regimen.

Living with pulmonary artery hypertension: patients' experiences.

BACKGROUND: Research on the outcomes of medical therapy in persons with pulmonary artery hypertension (PAH) has increased as new therapeutic options have emerged. Little investigation has been done on the impact of living with PAH despite inferences that quality of life (QOL) improves. PURPOSE: The purpose of this qualitative study was to describe patient experiences of living with PAH and identify factors that may have an impact on QOL. PARTICIPANTS: Participants (n = 11; 8 women, 3 men) were selected from among 42 adult patients, 40 to 72 years of age, followed in an outpatient setting at a tertiary care hospital. Multiple types of treatment modalities were represented including calcium channel blockers, endothelin-receptor antagonists, prostacyclin analog, and lung transplantation. METHODS: Semistructured interviews allowed participants to describe experiences living with PAH. Interviews were recorded on audiotape and transcribed verbatim. Analysis was conducted in accordance with Colaizzi's 7-step process for analysis of phenomenologic data. RESULTS: Two overarching themes emerged indicating that participants experience uncertainty associated with a variety of aspects of this illness but also learn to cope with this uncertainty and move on with their lives. IMPLICATIONS: Assisting patients to cope with the uncertainty associated with this chronic health problem is essential if patients are to successfully adjust to the demands of the illness and its treatment. Attention to the findings of this study should guide health care professionals in their efforts to improve QOL in this patient population.

Surveillance Endomyocardial Biopsy in the Modern Era Produces Low Diagnostic Yield for Cardiac Allograft Rejection.

BACKGROUND: The changing epidemiology of cardiac allograft rejection has prompted many to question the yield of surveillance endomyocardial biopsy (EMB) in heart transplantation (HT) patients. We sought to determine the yield of EMB in the modern era. METHODS: We evaluated 2597 EMBs in 182 consecutive HT patients who survived to their first EMB. The EMBs were categorized as asymptomatic or clinically driven and were compared based on era of antiproliferative therapy use at our center (early azathioprine era: 1990-2000 vs modern mycophenolate era: 2000-2011). RESULTS: In the modern era, patients had a higher prevalence of risk factors for developing rejection (≥ International Society of Heart and Lung Transplantation grade 2R); however, the frequency of rejection was decreased at all times (0-6 months: 60.2% vs 21.5%, P < 0.001, 6-12 months: 26.8% vs 1.8%, P < 0.001, 12-36 months: 32.3% vs 10.5%, P = 0.006). The yield of asymptomatic EMB decreased in the modern era between 0 and 6 months (10.9% vs 3.12%), 6 to 12 months (17% vs 0%), and years 2 to 3 (6.1% vs 1.5%). In the early era, the odds ratio of rejection during asymptomatic EMB compared to a clinically driven EMB was 0.47 (95% confidence interval, 0.31-0.71) and was decreased in the modern era (0.17 [0.07-0.42], P = 0.04). The probability of detecting rejection on asymptomatic EMB was significantly reduced in the modern era, even after adjustment for tacrolimus and induction therapy (1% vs 8%, P < 0.001). CONCLUSIONS: The clinical yield of surveillance EMB has decreased in the modern era. The EMB in asymptomatic patients longer than 6 months after HT warrants further scrutiny.

Lifestyle and quality of life in long-term cardiac transplant recipients.

BACKGROUND: The purposes of this study were to describe long-term (>1 year) cardiac transplant recipients' perceptions of barriers to health-promoting behaviors; ability to manage their health, health-promoting lifestyle, health status and quality of life (QOL); and determine predictors of QOL. METHODS: Data were collected from 93 recipients who completed a self-report questionnaire incorporating: (1). patient characteristics; (2). barriers to health promotion, perceived health competence and health-promoting lifestyle; (3). perceived health status; and (4). QOL. All instruments used had acceptable reliability and validity. Objective measures of health status were retrieved from medical records. Data were analyzed using descriptive and comparative statistics, measures of association and multiple regression. RESULTS: Recipients were uncertain about their ability to manage their health; felt that barriers sometimes interfered with engaging in health-promoting behaviors; and often included health-promoting behaviors in their lifestyle. They rated their health as good and were moderately satisfied with life. Predictors of better perceptions of QOL included less education, longer time since transplant, ischemic etiology of heart failure, fewer barriers, higher perceived health competence and a health-promoting lifestyle (R(2) = 0.51; F = 14.77; p = 0.001). CONCLUSIONS: The present results provide information regarding factors that contribute to perceptions of quality of life after cardiac transplantation, have implications for identifying patients at risk for poor QOL, and sensitize clinicians to the need for ongoing patient education.

Evidence for racial disparity in cardiac transplantation survival rates.

Studies show that survival rates of cardiac transplantation are lower for African American transplant recipients than for Caucasians. Due to similarities in terms of etiology, treatment modalities and responses to these modalities, the authors examine some potential variables for survival of cardiac transplantation that have been well documented in both the renal transplantation literature and the medically managed congestive heart failure literature. The authors also discuss access to care, socioeconomic factors and immunological differences in attempting to identify relevant factors for survival of cardiac transplantation.

Psychosocial assessment of candidates and risk classification of patients considered for durable mechanical circulatory support.

BACKGROUND: The psychosocial assessment of candidates for transplantation (PACT), developed to assess candidates for heart transplant, has not been routinely used to assess left ventricular assist device (LVAD) candidacy. We examined the efficacy of the PACT to assess psychosocial outcomes in LVAD patients. METHODS: We reviewed patients who received LVAD implants between June 2006 and April 2011 and retrospectively applied the PACT. We determined the accuracy of identifying social success with the PACT and revised domains to reflect criteria influencing social success for LVAD patients. RESULTS: Forty-eight patients (72% men, 44% non-white, 50.4 years old) were divided into high-scoring and low-scoring groups. Nine patients with low PACT scores were falsely categorized as high-risk, whereas 4 with high scores had poor social outcomes. The score had a high positive-predictive value (0.86) but low negative-predictive value (0.31). The PACT was revised (modified [m]PACT) to measure indicators, such as social support and understanding of care requirements, identified to more closely affect LVAD outcome. The mPACT exhibited improved accuracy. A reclassification table was developed, and the net reclassification index was 0.32. The percentage of patients incorrectly classified for social risk decreased from 27% with the PACT to 8% with the mPACT. Patients with higher mPACT scores had decreased 30-day readmission rates (26% vs 67%, p = 0.045) after device implantation. CONCLUSIONS: By emphasizing social support, psychologic health, lifestyle factors, and device understanding, the mPACT showed improved performance in risk-stratifying candidates for LVAD therapy. Prospective validation is warranted.